P672 Switching out of class or to another anti-TNF agent is the most effective strategy in IBD patients with immunogenicity against anti-TNF antibodies

Abstract Background Immunogenicity to anti-TNF agents is associated with loss of response in inflammatory bowel disease (IBD). However, the efficacy of different strategies to restore favourable pharmacokinetics and/or clinical response upon the detection of anti-drug antibodies (ADA) has not been widely studied. We evaluated the success of different strategies leading to clinical remission with ADA disappearance (in patients continuing the same anti-TNF), in patients with IBD. Methods IBD patients with ADA to infliximab or adalimumab were identified through an electronic database search at a single tertiary centre between 2004 and 2021. ADA were measured using a drug-sensitive assay at Sanquin laboratories. Data concerning clinical, biochemical and endoscopic activity, medication and surgery were retrospectively and systematically collected by reviewing clinical records. Criteria for success of a strategy were clinical remission 1 year after ADA detection without further change in strategy combined with disappearance of ADA (in patients continuing the same anti-TNF). Results Two-hundred-and-fifty-five IBD patients (206 Crohn’s disease, 46 ulcerative colitis, 3 IBD-unclassified, 149 female) were included, 129 patients were diagnosed to have ADA against infliximab and 126 against adalimumab. At baseline, median ADA titer was 77 AU/ml (IQR 25-350), 50.2% of patients were in clinical remission. Groups were as follows: 1) 81/255 (32%) conservative management, 2) 102/255 (40%) optimization of the same anti-TNF, 3) 72/255 (28%) switch to another anti-TNF or biological class. Switch to another anti-TNF or out of class was the most successful strategy in terms of improvement of clinical remission (from 19.4% at ADA detection to 69.4% at 1 year, p<0.001). Patients that continued with the same dose anti-TNF or discontinued all biological therapy after ADA detection were often in clinical remission at baseline, but deteriorated significantly in the following year (22.7%, P=0.004). Anti-TNF dose intensification with concomitant addition/optimisation of immunomodulators was the fastest (median 3 months (IQR 2-4.5), p=0.004) and most effective (in 73% of these patients, p=0.007) strategy to suppress ADA to undetectable levels compared to anti-TNF dose intensification or immunomodulator optimization alone. Conclusion Switching to another anti-TNF or out of class switch is the most successful strategy to regain and maintain clinical remission upon detection of ADA. Intensification of anti-TNF dosing with concomitant optimisation of immunomodulatory therapy is the fastest strategy to suppress ADA.